Crystal Deposition Disease Flashcards
Gout
Etiology & Epidemiology
the metabolsim of uric acid
Epi
- most common form of inflammatory arthritis as an inflammatory response to the tissue deposition of monosodium urate crystals (uric acid) within the joint
- uncommon to happen before menopause in women, men > women & a disease that increases with age
Etiology
- hyperuricemia (increased uric acid) is necessary aspect of gout, but not the only risk factor for developing it
- the increase in uric acid within the blood (hyperuricemia) leads to deposition of these crystals in areas of low blood flow– joints and kidneys!
Uric Acid Metabolism
- urica acid is the byprodct of purine and pyramidine (DNA breakdown) metabolism
- these molecules breakdown into uric acid: but only have a limitied soluablity in the blood
- so if theres too much of them, thew wont all be able to dissolve into the blood andbe extreting into the urine = crystal formation = gout
Adenosine and Guanosine are the AA which breadown into Xanthine –> uric acid –> allontoic acid
(this porcesses needs xanthine oxidase as an enzyme to happen
(this process also needs HGPRT early on, something which some people are deficient/born withou)
what are some ways in which hyperuricemia can be developed wihtin the body
overproduction & underexcretion
medications which can cause gout
Overproduction of Purines
- high cell turnover states: malginacy, hemolytic anemia, exercise
- dietary: red meats, organ meats, seafood
- obesity & insulin resistnace
- specific genetic conditions
Underexcretion (90% of the issues are here)
- dehydration : big reason
- renal insufficiency, HTN, obestiy and insulin resistance
MEDICATIONS
C: cyclosporines
A: alcohol
N: nicotinic acid
T: thiazide diuretics!!!
L: LASIX- diuretics
E: Ethambutol
A: Asprin
P: Pyranzimide
History: how does hyperuricemia cause gout and why doesnt everyone with hyperuricemia get gout
Asymptomatic Hyperuricemia: those without symptoms of increased uric acid levels within the blood
defined as the level of 7-8
- guidlines suggest NOT TREATING asymptomatic hyperuricemia (despite the signifcant increase in the risk of gout developing)
overtime, this increase in hyperuricemia rises, and the uric acid cant dissolve = crystals in the body in the joints and the kidneys
crystals = monosodium urate crystal deposition
Articular Monosodium Urate Crystal Depostion –> Acute Gout
over time, recurrent acute gout = chronic gout
over time, chronic gout = topaceous gout: hard, depostiions of the crysatals in extraaarticular places
Gout: Symptoms and Presentation
acute gout
Acute
- monoarticular (initial episode) inflammatory arthritis : 1st MTP is the joint most often invovled: the “Podagra”
- this is a rapid onset of swelling in the joint: redness, warmth, & swelling in less than 24 hours
- the pain is so bad that non-painful things trigger pain: like bedsheets!
- this acute attacks are typically self-limiting (resolve within about 1 week) but we clinical treat instead of self resolving
other joint locations
- 1st MTP is MC
- foot and ankle
- knee
- elbow
- rarely: shoudler, fingers and wrist
Gout: Sympttoms and Presentaion
Tophi
Tophi
- the extra-articualr manifestations of gout
- usually a late finding (assocaited with chronic gout i think)
Monsodium Urate Crystals deposit in….
- the joint
- connective tissue locations (ear lobs, olecranon bursa on elbow)
- nephrolithlasis: kidney stones which develop from the increase uric acid
- renal interstital (gouty nephropathy)
Diagnosis of Gout
how is it dx.
in serum v in synovial fluid
synovidal fluid
- the gold standard dx. BUT , not necessary to make the dx. : can be a clinical dx. with acute onset, typical location & good history
Findings…
- uric acid crystals
- inflammatory cell count: (2.5 - 50k+ WBC, with neutrophil predominance most often)
- cloduy, purulent fluid
- negative culutre and gram stain (r/o septic)
Serum
- uric acid is most commonly normal during an acute attack : because its all in the joint
- elevated inflammatory markers (ESR, CRP)
- leukocytosis
- thrombocytosis
gout can co-exist with other inflammaotry or noninflammatory conidtions — always aspirate to be sure
Imaging Fingings in Gout on
Appearance of Crystals under microscopy
Radiographic
- nontophaceous: will appear normal or with effusion in the joint spaces
- tophaceous: sclerotic, periarticular erosins (these will be outside teh joint, in the soft tissue near the joint)
MSK Ultrasound
- double contour sign
- shiny”
Dural Energy CT scan
- green
__________________________ Microscopy
negative (blue) bifrefringent needle-shaped
- they are share, demarked lines that go against the direction of the polarized light
- can be intracellular: more specific for active gout
Treatment of Gout
Acute Management
Acute Management
- NSAIDS
- cholchicine
- Steroids
- Il-1 Antaonists (rarely)
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NSAIDS: first line but unfortunately these are RARELY give, becuase all the pts. with gout have co-morbidities contraindicating with NSAID use (CKD, CAD)
but if youre giving….
- any of them (ibuprofen, etc.) for 7-10 days
Cholchicine
- a microtubular inhibitor: the downside is that if this is not started early early on in the disease progression, it will rarely actually be benificial
narrow thearpeudic range: only effective after symptoms onselt (within 24 hours)
AVOID in ….
- CKD pt (not dilyzable)
- risk of inflam. myositis
Steroid Use
- Intra-articualr steroids: for mono-oligo (3 or less) joints
- intramuscular/oral: for polyarticualr disease
- need these to be longer than a taper pack, need longer
Treatment of Gout
Chronic Treatment
Chronic Treatment
- dietary, lifestyle changes
- Xanthine oxidase inhibitors: Allopurinol
- uricosuric
- recomb. uricase
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Dietary Changes
AVOID: organ/glandular meat & high fructose syrup
limit: red meat, anchovies, shellfish, fruit jucie & alcohol/beer
encourage: plant proteins, low fat dairy and water
Urate Lowering Therapies
XOI: allopurinol, febuxostat
Uricosurics: increase renal excretion
recombiant uricase: turn to allatonin to excrete
indications for using urate lowering meds
- FREQUENT FLARES: 2-3x in 1 year
- renal stones
- tophaceous gout
- moderate CKD
Chronic Gout Treatment: Allopurinol
must check what
dosing pearls
Allopurinol: type of XOI (which reduce the ability of xanthine oxidase to convert to uric acid
Guidelines
- anyone with the HLA-5801 gene at 100x risk of a hypersensitivity reaction to allopurinol (rapid onset of rahs, crsuting and skin conditions)
- must check an HLA-B5801 gener before adminstering in the following populationa…
- Han Chinese, Thai, Korean, AA
Dosing Peals
- dont stop allopurinol when hospitalzied or in an acute flare
- starting or restarting gout = higher time period of gout acute flare to occur
- thus, when starting the med NEED TO START ON A PROPHYLATIC LOW DOSE THERAPY
- low dose NSAID, chlchicin or low dose prednisone as you start it - keep on until levels are stable then, 2-3 months and can take off the prophylatic
Dosing GOals
- nontophaceous = uric acid < 6
- tophaceous = uric acid < 5
Uricosurics for Chronic Gout
(Probenacid)
Recombinar Uricase for Chornic Gout (Pegloticase)
Uricosurics: Probenacid
- rarely used, increases the proximal tubule excretion of uric acid
- only wokring if they have a baseline excertion which is low
- cannot use if GFR < 30 (CKD)
Recombinant Uricase: Pegloticase
- for those resistant to ULT or these with intractable tophi
- rapidly decrease in uric acid as it converts to allanotin
- IV infusions but rarely tolerated for long periods of time
- high allergy
Calcium Pyrophosphate Deposition Disease
Etiology
(CPPD) : “pseudogout”
Etiology
- calcium salt that is in crystalline form deposits in the cartialge and other articualr tisses
- cannot be measured in the serum: unlike uric acid
- a group of disease sattes: XR, Chronic CPPD arthritis “psuedorheum” and OA with CPPD)
Imaging Findings
- Chondrocalcinosis: calcification of the articular hylaine cartilage
- see “hazy” within the joint space
- CPPD is the MCC of the chondrocalcinosis you will see
CPPD specifically
- a disease primarily seen in thsoe > 85
- assocaited with many other diseases (hyperparathyroid, hemochromatosis, mypomagnesia, wilsons’disease, OA, privious joint issues)
CPPD: clinical presenations
CPPD presents very similar to gout
Joint’s impacted: knees and wrists most common
- can be elbows, ankles, shoulders and others
- mocks sepsis as it is incredibly inflammatory
- confusion in the eldery
Diagnosis
- cannot be diagnosed without a joint aspiration!!!!
- CPPD crystals will be on microscopy….
- weakly positive to bi-firengent, polymorphic rhomoid crystals
- so they’re multiple shapes of the crystals & they’re aligned with the light & blue
- ABC: aligned, blue, CPPD, therefore if they’re nonaligned and blue = gout
CPPD Treatement
Treatment
- treat secondary conditions
ACute treatment
- similar to gout
- steroids (favor local like topical over systemic)
- NSAIDS
- Chochicine
Chronic treatment
- can use low dose daily cholchicine
